We have previously shown that patients with systemic mastocytosis have elevated plasma histamine levels without the problems demonstrated in normal volunteers infused with histamine to a similar blood level. In an effort to determine how the body adapts to elevated histamine levels, we have examined end organ responses to histamine, and in the case of the skin, to the mast cell degranulator, codeine. It now appears that both the skin and lungs have normal dose response curves to histamine, and in the case of the skin, to codeine, when compared to normal subjects. Thus, patients with mastocytosis do not exhibit end organ desensitization to histamine, but adapt to increased histamine levels via an alternative mechanism. Cells with ultrastructural features of basophils may be observed in cultures of marrow from patients with mastocytosis. These cells are toluidine blue positive, contain histamine, and degranulate to the calcium ionophore A23187. Such cells increase in number under the influence of supernatants taken from cultures of human peripheral blood mononuclear cells stimulated wtih concanavalin A.